Molecular basis for functional connectivity between the voltage sensor and the selectivity filter gate in Shaker K+ channels

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Abstract

In Shaker K⁺ channels, the S4-S5 linker couples the voltage sensor (VSD) and pore domain (PD). Another coupling mechanism is revealed using two W434F-containing channels: L361R:W434F and L366H:W434F. In L361R:W434F, W434F affects the L361R VSD seen as a shallower Q-V curve that crosses the G-V. In L366H:W434F, L366H relieves the W434F effect converting a non-conductive channel in a conductive one. We report a chain of residues connecting the VSD (S4) to the selectivity filter (SF) in the PD of an adjacent subunit as the molecular basis for voltage-sensor selectivity filter gate (VS-SF) coupling. Single alanine substitutions in this region (L409A, S411A, S412A or F433A) are enough to disrupt the VS-SF coupling, shown by the absence of Q-V and G-V crossing in L361R:W434F mutant and by the lack of ionic conduction in the L366H:W434F mutant. This residue chain defines a new coupling between the VSD and the PD in voltage-gated channels.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

1. Carvalho-de-Souza and Bezanilla
(2018) Nonsensing residues in S3-S4 linker's C terminus affect the voltage sensor set point in K+ channels.
Fig 2B.

https://cdn.elifesciences.org/articles/63077/J Gen Physiol 150:307-322.

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Carlos A Z Bassetto Jnr

Biochemistry and Molecular Biology, University of Chicago, Chicago, United States

Competing interests
The authors declare that no competing interests exist.
João Luis Carvalho-de-Souza

Department of Anesthesiology, University of Arizona, Tucson, United States

Competing interests
The authors declare that no competing interests exist.
Francisco Bezanilla

Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States

For correspondence
fbezanilla@uchicago.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6663-7931

Funding

National Institutes of Health (R01-GM030376)

Francisco Bezanilla

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institution of animal care and use committee (IACUC) protocols (#71745) of the University of Chicago.

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